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干货分享 | 淋巴细胞和NK细胞，是如何生成的？
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淋巴细胞和NK细胞的生成 Lymphocyte and NK Cell Production CLP被认为能产生B淋巴细胞、T淋巴细胞和NK细胞。骨髓中B淋巴细胞和T淋巴细胞祖细胞的发育与抗原无关。SCF和Flt3L似乎都参与了小鼠早期淋巴系祖细胞的生成。 The CLP is believed to give rise to B lymphocytes, T lymphocytes, and NK cells.16 The development of B lymphocyte and T lymphocyte progenitors in bone marrow is antigenindependent. Both SCF and Flt3L appear to be involved in the production of early lymphoid progenitor cells in mice. B淋巴细胞祖细胞在大多数哺乳动物的骨髓中，在犬、猪和反刍动物的佩耶氏结中，以及在鸟类的法氏囊中生成成熟的、未成熟的B淋巴细胞。 大约2到3天，前B淋巴细胞在骨髓中发育为成熟的幼稚B淋巴细胞并进入循环。在骨髓中生成的B淋巴细胞中，只有不到20%成为外周成熟B淋巴细胞池的一部分，大多数细胞在骨髓或进入血液后被淘汰，B淋巴细胞也可以在成年动物外周血的淋巴组织中增殖。 与其他血细胞一样，骨髓和淋巴器官的微环境对淋巴细胞的生成很重要。抗原敏感的表面免疫球蛋白阳性B淋巴细胞的生成以免疫球蛋白基因位点的连续重排和表面蛋白的选择性表达为标志。 尽管许多细胞因子（包括SCF、Flt3L、SDF-1和IGF）参与骨髓中B淋巴细胞的生成，但IL-7似乎是一个特别重要的正生长因子。B淋巴细胞的生成受到多种因素的抑制，包括TGF-β、IFN-α、IFN-β和IFN-γ。 B lymphocyte progenitors produce mature, naive B lymphocytes in the marrow in most mammals, in specialized ileal Peyer’s patches in dogs, pigs, and ruminants, and in the bursa of Fabricius in birds. Approximately 2 to 3 days arerequired for pre-B lymphocytes to develop into mature, naive B lymphocytes in the marrow and enter the circulation. Less than 20% of B lymphocytes produced in the marrow become part of the peripheral mature B lymphocyte pool, with most of the cells being culled in the bone marrow or after their entry into blood. B lymphocytes also proliferate in peripheral lymphoid tissues in adults. As with other blood cells, the microenvironment of the marrow and lymphoid organs is important for lymphopoiesis. The production of antigen-sensitive, surface-immunoglobulin-positive B lymphocytes is marked by successive rearrangements of the immunoglobulin gene loci and selective expression of surface proteins. Although a number of cytokines—including SCF, Flt3L, SDF-1, and IGF—are involved in B lymphocyte production in marrow, IL-7 appears to be an especially important positive growth factor. B lymphocyte lymphopoiesis is inhibited by several factors, including TGF-β, IFN-α, IFN-β, and IFN-γ. 哺乳动物次级淋巴器官T淋巴细胞区的抗原刺激可以激活循环B淋巴细胞，然后迁移到淋巴结、佩耶氏结和脾脏的滤泡。B淋巴细胞的活化和分化为浆母细胞，是由微生物产物、细胞因子和结合在T淋巴细胞和树突状细胞表面分子组合诱导的。浆母细胞可以在生成它们的淋巴器官中发育为浆细胞，也可以通过血液迁移并在周围组织或骨髓中发育为浆细胞。SDF-1将循环浆母细胞吸引到骨髓，包括SDF-1和IL-6在内的因子通过阻止细胞凋亡来促进浆细胞的发育。 Recirculating B lymphocytes are activated by antigenic stimulation in the T lymphocyte region of secondary lymphoid organs, followed by migration to the cortex in lymph nodes and to follicles in jejunal Peyer’s patches and the spleen in mammals. B lymphocyte activation and differentiation into plasmablasts is induced by combinations of microbial products, cytokines, and molecules bound to the surfaces of T lymphocytes and dendritic cells. Plasmablasts can develop into plasma cells in the lymphoid organs where they are produced or can migrate through blood and develop into plasma cells in peripheral tissues or bone marrow. SDF-1 attracts circulating plasmablasts to the bone marrow, and factors including SDF-1 and IL-6 promote plasma cell development by preventing apoptosis. T淋巴细胞祖细胞离开骨髓，迁移到胸腺。这些细胞的归处取决于它们与胸腺内皮细胞上各种粘附分子的相互作用以及胸腺基质细胞生成的特异性趋化因子。 T淋巴细胞祖细胞在胸腺微环境和胸腺产生的生长因子(包括Flt3L和IL-7)的影响下发育成T淋巴细胞。哺乳动物胸腺成熟后，T淋巴细胞会聚集在淋巴结皮质旁区、脾脏小动脉周围淋巴结和佩耶氏结滤泡间区。 T lymphocyte progenitors leave the marrow and migrate to the thymus. Homing of these cells to the thymus depends on their interaction with various adhesion molecules on thymic endothelial cells and the production of specific chemotactic factors by thymic stromal cells. T lymphocyte progenitors develop into T lymphocytes under the influence of the thymic microenvironment and growth factors (including Flt3L and IL-7) produced in the thymus. After maturation in the thymus, T lymphocytes accumulate within paracortical areas of lymph nodes, periarteriolar lymphoid sheaths of the spleen, and the interfollicular areas of jejunal Peyer’s patches in mammals. 大多数NK细胞是由骨髓中的祖细胞生成的，它们在骨髓中经过一周或更久时间的扩增和成熟，然后释放到血液中。控制其产生的生长因子需要进一步的表征，但SCF、IL-2、IL-7和IL-15可以在体外刺激NK细胞从祖细胞发育而来。NK细胞亚群也在胸腺和其他可能的器官，如淋巴结、肝脏和脾脏中发育。这些部位可能依赖于骨髓来源的祖细胞和/或未成熟的NK细胞从血液中进入这些器官，它们在微环境的影响下成熟。 Most NK cells are produced from progenitor cells in the bone marrow, where they undergo expansion and maturation for a week or more before their release into the blood.Growth factors controlling their production need further characterization, but SCF, IL-2, IL-7, and IL-15 can stimulate NK cell development from progenitor cells in vitro.Subsets of NK cells also develop in the thymus and possibly other organs, such as lymph nodes, liver, and spleen. These sites may depend on the trafficking of bone marrow–derived progenitor cells and/or immature NK cells into these organs from the blood, where they mature under the influence of microenvironmental factors. |
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